Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset
Authors: Haiqing Song, Yuan Wang, Qingfeng Ma, Wuwei Feng, Rui Liu, Xiaomei Lv, Lijuan Huang, Yifan Li, Yi Yang, Deqin Geng, Jianguo Zhu, Yan Wei, Huisheng Chen, Runxiu Zhu, Qijin Zhai, Jing Guo, Bo Liu, Shigang Zhao, Yuping Wang, Yongqiu Li, Yanyong Wang, Cunju Guo, Li Guo, Xueshuang Dong, Baojun Wang, Jianfeng Wang, Aiqin Dong, Congmin Ma, Zhuobo Zhang, Xiangyang Tian, Hong Yang, Hongliang Dong, Yan Wang, Fei Yi, Xiaoping Jin, Chun Wang, Yansong Li, Yiping Wu, Jie Lin, Wei Yue, Huishan Du, Fanhua Meng, Guozhong Li, Yun Xu, Qiumin Qu, Hongbin Sun, Hong Tan, Jin Han, Shuiping Zhou
Journal: JAMA Network Open (2023)

Importance Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS). Objective To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS. Design, Setting, and Participants This randomized, alteplase-controlled, open-label, phase 3 clinical trial was conducted from May 2018 to May 2020 at 35 medical centers in China. A total of 684 patients were screened and 674 patients were enrolled. Included patients were aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. Data were analyzed from June to October 2020. Interventions Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase. Main Outcomes and Measures The primary objective was to assess whether rhPro-UK was noninferior to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days. Results Among 663 patients in the modified intention-to-treat population (mean [SD] age, 61.00 [10.20] years; 161 females [24.3%]), there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group. The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00). There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up. The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group (risk difference, 0.89; 95.4% CI, −6.52 to 8.29). Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group ( P &amp;amp;gt; .99). Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients [42.2%]) than the rhPro-UK group (85 patients [25.8%]) ( P &amp;amp;lt; .001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) ( P &amp;amp;gt; .99). Conclusions and Relevance This study found that intravenous rhPro-UK within 4.5 hours of AIS onset was noninferior to alteplase. The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group. Trial Registration ClinicalTrials.gov Identifier: NCT03541668